{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:34:10Z","timestamp":1792056850710,"version":"4.4.0"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T00:00:00Z","timestamp":1543536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NEI EY011915 (SCP), NIH\/NEI EY026893 (CSDP), EY08512 (MAS), and EY021784 (MAS)."],"award-info":[{"award-number":["NEI EY011915 (SCP), NIH\/NEI EY026893 (CSDP), EY08512 (MAS), and EY021784 (MAS)."]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Decreased corneal innervation is frequent in patients with Sj\u00f6gren Syndrome (SS). To investigate the density and morphology of the intraepithelial corneal nerves (ICNs), corneal sensitivity, epithelial cell proliferation, and changes in mRNA expression of genes that are involved in autophagy and axon targeting and extension were assessed using the IL-2 receptor alpha chain (CD25 null) model of SS. ICN density and thickness in male and female wt and CD25 null corneas were assessed at 4, 6, 8, and 10\/11 wk of age. Cell proliferation was assessed using ki67. Mechanical corneal sensitivity was measured. Quantitative PCR was performed to quantify expression of beclin 1, LC3, Lamp-1, Lamp-2, CXCL-1, BDNF, NTN1, DCC, Unc5b1, Efna4, Efna5, Rgma, and p21 in corneal epithelial mRNA. A significant reduction in corneal axon density and mechanical sensitivity were observed, which negatively correlate with epithelial cell proliferation. CD25 null mice have increased expression of genes regulating autophagy (beclin-1, LC3, LAMP-1, LAMP-2, CXCL1, and BDNF) and no change was observed in genes that were related to axonal targeting and extension. Decreased anatomic corneal innervation in the CD25 null SS model is accompanied by reduced corneal sensitivity, increased corneal epithelial cell proliferation, and increased expression of genes regulating phagocytosis and autophagy.<\/jats:p>","DOI":"10.3390\/ijms19123821","type":"journal-article","created":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T12:13:17Z","timestamp":1543579997000},"page":"3821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Reduced Corneal Innervation in the CD25 Null Model of Sj\u00f6gren Syndrome"],"prefix":"10.3390","volume":"19","author":[{"given":"Mary Ann","family":"Stepp","sequence":"first","affiliation":[{"name":"Department of Anatomy and Regenerative Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA"},{"name":"Department of Ophthalmology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonali","family":"Pal-Ghosh","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Regenerative Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gauri","family":"Tadvalkar","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Regenerative Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3980-0457","authenticated-orcid":false,"given":"Alexa R.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Regenerative Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Pflugfelder","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9057-5494","authenticated-orcid":false,"given":"Cintia S.","family":"De Paiva","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.autrev.2014.10.012","article-title":"Regulatory T-cells in autoimmune diseases: Challenges, controversies and\u2014yet\u2014unanswered questions","volume":"14","author":"Grant","year":"2015","journal-title":"Autoimmun. 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